PT  - JOURNAL ARTICLE
AU  - Qian, Yan
AU  - Li, Xin
AU  - Li, Guiliang
AU  - Liu, Huali
AU  - Li, Qiaofen
AU  - Liu, Xia
AU  - Zhang, Yang
AU  - He, Zongying
AU  - Zhao, Ying
AU  - Fan, Hong
TI  - Astrocyte-Derived Exosomal miR-148a-3p Suppresses Neuroinflammation and Restores Neurological Function in Traumatic Brain Injury by Regulating the Microglial Phenotype
AID  - 10.1523/ENEURO.0336-23.2024
DP  - 2024 Feb 01
TA  - eneuro
PG  - ENEURO.0336-23.2024
VI  - 11
IP  - 2
4099  - http://www.eneuro.org/content/11/2/ENEURO.0336-23.2024.short
4100  - http://www.eneuro.org/content/11/2/ENEURO.0336-23.2024.full
SO  - eNeuro2024 Feb 01; 11
AB  - Interactions between astrocytes and microglia play an important role in the regeneration and repair of traumatic brain injury (TBI), and exosomes are involved in cell–cell interactions. A TBI model was constructed in rats. Brain extract (Ext) was isolated 1 d after TBI. Astrocyte-derived exosomes were obtained by coculturing Ext with primary astrocytes, and the morphology of exosomes was observed by electron microscopy. The isolated exosomes were cocultured with microglia to observe phenotypic changes in M1 and M2 markers. Aberrant RNA expression was detected in necrotic brain tissue and edematous brain tissue. The role of miR-148a-3p in regulating microglial phenotype was explored by knocking down or overexpressing miR-148a-3p. Finally, the effect of miR-148a-3p on TBI was studied in a rat TBI model. Astrocyte-derived exosomes stimulated by Ext promoted the transition of microglia from the M1 phenotype to the M2 phenotype. MiR-148a-3p was highly expressed in TBI. Transfecting miR-148a-3p promoted the transition of microglia from the M1 phenotype to the M2 phenotype and inhibited the lipopolysaccharide-induced inflammatory response in pre-microglia. In a rat TBI model, miR-148a-3p significantly improved the modified neurological severity score and attenuated brain injury, which promoted the transition of microglia from the M1 phenotype to the M2 phenotype. MiR-148a-3p alleviated TBI by inhibiting the nuclear factor κB pathway. Astrocyte-derived exosomal miR-148a-3p regulates the microglial phenotype, inhibits neuroinflammation, and restores neurological function in TBI. These results provide new potential targets for the treatment of TBI.